Field of Invention
The present invention relates to a carrier for a topical medicament having improved ability to penetrate thick keratinous tissues, a topical anti-fungal composition useful for the treatment of dermatophytes infection in the nail bed and nail plate and a method for treating fungal nail infections using the composition.
Discussion of the Background
Dermatophytes are filamentous fungi that are commonly found in plants and soil. Nail invasion by these organisms cause disease, with thickening, discoloration, odor, decay, lysis (loosening of the nail plate from the base of the nail bed), and deformity such as increased curvature of the nail plate. In addition to dermatophytes, candida albecans (a yeast) is also a common pathogen. A small number of diseases are also caused by molds, considered non-dermatophytes. The medical name for fungal nail disease is onychomycosis. Fungi live in the nail bed under the toenail and also involve the nail itself. The fungus is a parasite, and lives on the keratin, by dissolving the keratin with enzymes known as keratinases. The most common organisms are Trichophytan Rubrum (which causes between 80-90% of infections), Trichophytan Mentagrophytes, Epidermophytan Floccosum and Candida Albecans.
Many times the fungi will cause the nail to produce excess keratin, a condition known as hyperkeratosis, causing the nail to be thicker and often deformed. Additionally, the thicker toenail can cause pain, leading to ingrown nails, and even difficulty in wearing shoes due to the thickness. The typical treatment for this condition involves having a podiatrist debride or manually thin the nail, often at great cost to the patient, insurance, and Medicare.
The cells in the nail are connected by a intercellular phospholipid connections called desmosome. To effectively treat onychomycosis, it is necessary to get the antifungal medicine through the nail plate and keratin, which may be very thick, and penetrate to the site where the organism lives.
One U.S. study suggested a prevalence of Onychomycosis of 18.5% with the number of persons affected on the rise, which may be partly accounted for by the aging U.S. population. Onychomycosis affects 32% of the people between 60-70 years of age, and some studies suggest it may affect 48% of the population by age 70. Onychomycosis has a stronger prevalence in immunosuppressed people, such as those with diabetes, poor circulation, or HIV infection. Toenail infections are several times more common than fingernail infections. Several oral medicines are effective in treating these conditions, such as Lamisil and Sporonox. However, these medicines are prescription medications, costing the patient as much as $1000 to treat an infection, and requiring extraneous lab tests, because they can cause damage to the liver and kidneys as well as other side effects.
Topical treatments have historically been somewhat ineffective. According to the Physicians Desk Reference, antifungals used for skin, such as terbinafine (Lamisil), Ciclopirox Olamine and tolnaftate, are not indicated topically for fungal toenails because they don't penetrate. While Ciclopirox Olamine is FDA approved for toenail, it is in a water soluble lacquer (Penlac) and therefore doesn't penetrate more than approximately 0.4 mm through the large toenail. Because of this, Penlac requires monthly treatments by the doctor to debride or remove the dead nail tissue and is expensive (with a small bottle of 6 cc costing typically over $150). Additionally it is only indicated for disease of the nail distal to the lunula-white half moon. According to the Physician's Desk Reference (PDR), studies using Penlac indicate only about a 10% cure rate and about 50% improvement. Further, the PDR states that Penlac is not effective against the most common fungus to infect nails, Trichophytan Rubrum.
In order to get effective concentrations of terbinafine, it is necessary to administer it orally. The pills are often expensive and require doctor's visits to monitor liver toxicity. One in 500 patients has a serious reaction to the drug. In addition to this, there is a 15% reoccurrence of the fungal toenail in the first year. There are other OTC medicines but proof of their efficacy is difficult to determine.